Certain 3-phenyl-5-alkyl-1, 2, 4-oxadiazoles, substituted in the phenyl ring



United States Patent 3,270,029 CERTAIN 3 PHENYL ALKYL-1,2,4-OXA-DlAOLES, SUBSTITUTED IN THE PHENYL RlN Giuseppe Palazzo, Rome, Italy,assignor to Aziende Chimiche Riunite Angelini Francesco, Rome, Italy NoDrawing. Filed Jan. 2, 1964, Ser. No. 335,402 Claims priority,application Italy, Jan. 7, 1963, 193/63 15 Claims. (Cl. 260-307) Thepresent invention relates to 3-phenyl-5-alkyl-l,2,4- oxadiazoles, whichare substituted in the phenyl ring and whose general formula is:

I R N=C-A1kyl in which R (which may occupy any of the ortho, meta andpara positions) is a radical that is liable to convert the compound to awater soluble salt, and precisely a radical chosen from the group: -OH,COOH, -NH N(CH -SO H, SO NH SO NHR, SO NR NH-NH NHCN, NH-C(NH)NH or anitro group or an ureido or a thio-ureido group, and alkyl is a loweralkyl radical having 1 to 4 carbon atoms.

These compounds present analgetic and antiphlogistic activities.

A method for preparing the compounds of the general Formula I involvesreacting anhydrides or chlorides of carboxylic acids withbenzamidoximes, which are substituted or not on the phenyl ring with Rgroups, and eventually said substituents are introduced in the phenylring after cyclization to an 1,2,4-oxadiazole.

Cyclization of a benzamidoxime, carrying radical R on the ring, with ananhydride or a chloride of an acid (the Tiemann reaction), according tothe following formula, is especially appropriate in case R does notreact with the acylating agent, and particularly when R is a nitrogroup.

NOH

R NH:

R =C-Alky1 Sulphamides also may be prepared according to said reactionbut the cyclization conditions must be adequately chosen in order toavoid acylation of the sulphamid group. Some nitro-derivates, as well assome sulphamides, differing from the compounds here claimed, are alreadydescribed in the literature, as obtained with the same reaction (seeSchopif, Berichte 18, 1066, 2473; Weise, Berichte 22, 2420; Ponzio eBusti, Gazz. Chim. Ital. 36, II, 340; Pinnow Saman, Berichte 29, 629).

Substituent R may be introduced in the 3-phenyl-5-alkyl-l,2,4-oxadiazole already formed, according to a variation of themethod. The conditions of nitration, sulphonation, andchlorosulphonation of 3-phenyl-5-alkyl- 1,2,4-oxa'diazole have beenstudied, and it was observed that the substitution occurs selectivelyand sometimes with optimate yields, in position meta:

(b) or fuming H1504 =C-Alkyl (c) or ClSOzOH 3,270,029 Patented August30, 1966 All claimed compounds, but carboxylic acids, may be preparedwith known methods from the nitroderivates obtained according to thepresent inventions method. (See Spilker, Berichte 22,2781; Chem.Berichte 24,833; Krone, Berichte 24,838; Paschen, Berichte 24,3675).

The reduction may be carried out with Raney nickel catalyst, accordingto a method not precedingly applied to these compositions, or else withNaI-IS; but also stannous chloride and zinc powder may be used to thisend, according to classical methods.

Amines give dimethylamino-derivatives by reductive alkylation as toEschweiler-Clarkes technique; by treatment with potassium cyanate aminesgive ureas; with thiocyanate the thio-ureido derivatives.

The other compounds claimed are obtained through diazonium chlorides,which give the corresponding phenols by hydrolysis. (crf. Andrews, Kingand Walker, Proc Roy. Soc. B 133, 20; Bergmann, Bendas e dAvilla, J.Org. Chem. 1864), the hydrazines by reduction, the sulphonyl chlorideswith sulphur dioxide treatment. Sulphonium acids are obtained fromsulphonyl chlorides through hydrolysis, and sulphamides from the samewhen treated with amines.

Obviously, the direct sulphonation and chlorosulphonation of preformed3-phenyl-5-alkyl-1,2,4-oxadiazoles is much more convenient.

Preparation of carboxylic acids (some of them are already known) iscarried out by forming an oxadi-azole ring according to the classicalschema starting from the car-bethoxybenzonitrile, and hydrolyzing theester according to the schema:

NOH i C% NHz OOOEt COOEt NO 3 I O 0 OH N=C-Alky The following examplesillustrate the inventions methods:

EXAMPLE 1 g. of crude p-nitrobenzamidoxime and 160 cc. of butyricanhydride are heated during one hour at C. The reaction product iscooled and filtered. By crystallization from hexane, 70 g. ofnitroderivatives M.P. 89 C. are obtained.

Analysis.-For C H N O 4.48. Cale: C, 56.65; H, 4.75.

EXAMPLE 2 3-p-nitrophenyl-5-bwtyl-l ,2,4-0vcadiazole Found: C, 56.60; H,

EXAMPLE 3 3 -m-ni lroplzenyl-S -ethy l-I ,2,4-oxaa'iazole Found: C,58.05; H, 5.52.

A mixture of 50 g. of benzamidoxime and 135 cc. of propionic anhydrideis heated to ebullition for two hours, cooled, and taken up with etherand dilute sodium hydroxide. The etheric layer is dried. After removingthe solvent, the residue is distilled.

There are obtained 50 g. of 3-phenyl-5-ethyl-1,2,4- oxadiazole (B.P. 104C. at 2.3 mm.).

50 g. of 3-phenyl-5-ethyl-1,2,4-oxadiazole are dissolved in 160 cc. ofconcentrated sulphuric acid while cooling with a freezing mixture.Keeping the temperature under C., 45 cc. of nitrating mixture,consisting in 3 parts by volume of concentrated H 50 and 2 parts byvolume of concentrated HNO are added.

Finally the mixture is poured cautiously into an iced solution of 350 g.of NaOH in 2 litres of water and taken up with ether. The organic layeris washed to neutrality and dried. By removing the solvent a solidresidue is obtained, which may be crystallized from petroleum ether, 32g. of product (M.P. 64-65 C.).

Analysis.For C H N O Found: C, 54.57; H, 4.12. Calc.: C, 54.79; H, 4.14.

EXAMPLE 4 3-p-aminophenyl-S-isobutyl-1,2,4-0xadiaz0le A solution of 0.03mols of 3-p-nitrophenyl-5-isobutyl- 1,2,4-oxadiazole in 50 cc. dioxaneis treated with 1.1 cc. Raney-nickel under 3 atm. of hydrogen.

The absorption reaches the theoric value after about eight hours. Thecatalyst is filtered off, and the solvent removed at reduced pressure.The residue is then treated with diluted HCl and after filtering 01finsoluble tarry material, is alkalized with NaOH and extracted withether. The etheric layer is dried, the solvent removed and the productdistilled.

3 p aminophenyl-S-isobutyl-1,2,4-oxadiazole boils at 135 C. at 0.1 mm.Yield 93%.

Analysis.For C H N O. N Found: 19.15. Calc.: 19.34.

The benzoyl derivative melts at 139.

EXAMPLE 5 3-p-aminophenyl-5-butyl-1,2,4-0xadiaz0le 39 g. of3-p-nitrophenyl-5-butyl-1,2,4-oxadi-az0le are dissolved in 400 cc. ofanhydrous dioxane and treated with 7 cc. Raney Nickel at 40 atm. ofhydrogen in an autoclave. The absorption reaches the theoric value aftera short time. The catalyst is filtered off, the solvent removed atreduced pressure and the residue is taken up with ether and diluted HCl.

The acid solution is decolored with charcoal and energetically cooled.The hydrochloride crystallizes and more material is recovered byconcentrating the mother solution.

26 g. of 3-p-aminophenyl-5-butyl-1,2,4-oxadiazole hydrochloride areobtained. The product, as crystallized from acetone, melts at 181 C.

Analysis.For C H C1N O. Cl Found: 14.14. Calc.: 13.98.

The free amine boils at 159 at 0.9 mm.

EXAMPLE 6 3-m-aminophenyl-S-ethyl-I ,2,4-0xadiaz0le In the first place,a hydromethanolic solution of NaHS is prepared from 50.5 g. of anhydroussodium sulphide, 16.6 g. of sodium bicarbonate, cc. of methanol and 102cc. of Water.

This solution, containing 11.8 g. of NaI-lS, is added to a boilingsolution of 29 g. of 3-m-nitrophenyl-5-ethyl- 1,2,4-oxadiazole in 1400cc. of methanol. The mixture is boiled 20 more minutes until 200 cc. ofthe solvent are distilled off.

It is then cooled and extracted with ether. The etheric solution istreated with HCl 1:1, the acid solution is treated with alkali and thebase is extracted with ether, and the ethereal solution is dried anddistilled. 3-maminophenyl-S-ethyl-1,2,4-oxadiazole boils at 143 C. at0.1 mm. Yield g. 19.5; the melting point of the hydrochloride is 175 C.

Analysis.For C10H12C1N3O. Calc.: 15.71.

C1 Found: 15.70.

EXAMPLE 7 3-p-aminophenyl-5 -propyl-1 ,2,4-oxadiazole A freshly preparedhydromethanolic solution of 20,6 g. of NaHS is added slowly to a boilingsolution of 3-p-nitrophenyl-5-propyl-1,2,4-oxadiazole in 350 cc.methanol. The mixture is then boiled during twenty minutes, until 500cc. of solvent are distilled off and is then cooled. 300 cc. of Waterare added to it. A liquid product is separated, which after washing withwater and drying weighs 44 g.

The crude 3-p-aminophenyl-5-propyl-1,2,4-0xadiazole is crystallized froma little benzene. 30 g. of the product melting at 88 C. are recovered.

Analysis.For C H N O. Found: C, 64.70; H, 6.22. Calc.: C, 65.00; H,6.45. The hydrochloride melts at 188 C.

EXAMPLE 8 3-p-dimethyl-aminophenyl-S-ethyl-I,2,4-0xadiazole 6.5 g. of3-p-aminophenyl-5-ethyl-1,2,4-oxadiazole are dissolved in 10 g. of 98%formic acid. 10 g. of 30% formaldehyde are added and the mixture isrefluxed during 16 hours.

It is then concentrated to dryness under reduced pressure. The residueis taken up with dilute HCl, freed from insoluble tarry residues byfiltering, cautiously alkalized with a 50% potassium carbonate solutionand finally extracted with ether.

The etheric layer is washed carefully, dried, and the solvent isremoved. A solid residue is obtained which crystallizes from methanol. 3g. of 3-p-dimethyl-aminophenyl-S-ethyl-1,2,4-oxadiazole M.P. 100 areobtained.

Analysis.For C H N O. Found: C, 66.07; H, 6.93; N, 19.03. Calc.: C,66.34; H, 6.96; N, 19.34. The hydrochloride melts at 193 (dec.)

EXAMPLE 9 3-p-ureid0-phenyl-5-is0butyl-1,2,4-0xadiaz0le 9 g. of3-p-aminophenyl-S-isobutyl-1,2,4-oxadiazole are dissolved into a slightexcess of dilute HCl. A concentrated aqueous solution of 7.6 g. ofpotassium cyanate is then added. After one night at room temperature themixture is extracted with ether, the extract dried, and the solventremoved. The residue, crystallized from benzene weighs 4.2 g. and meltsat C.

Analysis.For C H N O Found: N,21.68. Calc.: N, 21.35.

EXAMPLE 10 S-m-guanidinopheny l-5-ethyl-1,2,4-oxadiazole A mixture of 12g. of 3-m-aminophenyl-5ethyl-1,2,4- oxadiazole hydrochloride, 3 g. ofcyanamide and 45 cc. of absolute alcohol are refluxed during 12 hours.The solvent is removed at reduced pressure, the residue is taken up withwater, acidified with HCl to pH 4 and 5 decol-ored with charcoal,filtered and alkalized with NaOH.

A solid substance precipitates, and is crystallized from alcohol. 5.1 g.of M.P. 176 substance are obtained. The analytic sample of3-m-guanidinophenyl-S-ethyl- 1,2,4-oxadiazole melts at 178-80.

Analysis.-For C H N O. N Found: 30.42. Calc.: N, 30.29.

EXAMPLE 11 3-p-thioureidophenyl-S-methyl-I,2,4-00cadiaz0le Calc.

EXAMPLE 12 3-p-cyanamid0-phenyl-5-methyl-1,2,4-0xaaiaz0le A suspensionof 46.8 g. of 3-pthioureidophenyl-5- methyl-1,2,4-oxadiazole in 300 cc.of water is warmed 'to B.P.

There is added a boiling solution of 112 g. of KOH in water, andimmediately, under stirring, a hot solution of 88 g. of neutral leadacetate. The mixture is boiled during 5 minutes, and is cooled at Theprecipitate is filtered and extracted with a hot solution of dilute KOH.The liquids are mixed and cooled to the pH is made slightly acid byadding 125 cc. of acetic acid. The precipitate is filtered, washedthoroughly with water, dissolved in 250 cc. of KOH, filtered and againprecipitated with acetic acid. The precipitate is then washed, dried andcrystallized from 80% alcohol. 20.5 g. of 1613 melting substance arethus obtained. An analytical sample melts at 164.

Analysis.-For C H N O. Found: C, 59.71; H, 4.24; N, 28.23. Calc.: C,59.99; H, 4.03; N, 27.99.

EXAMPLE l3 3-p-hydroxyphenyl-5-ethyl-1,2,4-0xadiaz0le A solution of 4.5g. of sodium nitrite in 30 cc. of water is slowly added to a cooledsolution of 11.5 g. of 3-p-aminophenyl-5-ethyl-1,2,4-oxadiazole in 28cc. of concentrated HCl and 100 cc. of water.

The diazonium salt, as hereinbefore prepared, is hydrolyzed by warmingit together with a solution of 45 cc. of concentrated sulphuric acid in100 cc. of water. The precipitate is filtered and the product ispurified by taking it up with dilute alkali and precipitating it againby acidification. It crystallizes then from 35 cc. of acetic acid. 7 g.of 3-p-hydroxyphenyl-3-ethyl-1,2,4- oxadiazole, whose M.P. is 121, areobtained.

Analysis.-For C H N O Found: C, 63.05; H, 5.03. Calc.: C, 63.15; H,5.30.

EXAMPLE l4 3-p-hydrazinophenwlJ-propyl-1,2,4-ovcadiazole A solution ofsodium sulphite is prepared from 8.5 g. of NaOH in 65 cc. of water. Adiazonium salt solution is prepared by dissolving 8 g. of3-p-aminophenyl- 5-propyl-1,2,4-oxadiazole in 8 cc. of concentrated HCltemperature. Finally 40 cc. of concentrated HCl are added and themixture is cooled with a freezing mixture. The precipitate is filtered,dried and crystallized from alcohol. 4.5 g. of hydrochloride areobtained, which melts at 199 (dec.)

3 p hydrazino phenyl 5 propyl 1,2,4-oxadiazole is obtained by alkalizingthe hydrochloride; this compound, crystallized from methanol, melts at112-113.

Analysis.For C H N O. Found: C, 60.43; H, 6.54; N, 25.48. Calc..: C,60.53; H, 6.47; N, 25.67.

EXAMPLE 15 4-[3'(1 ,2',4'-oxadiazolyl-5'-propyl) benzenesulphonic acid Asolution of 40 g. of 3-p-a1minophenyl-5-propyl-1,2,4- oxadiazolehydrochloride in 35 cc. of concentrated HCl and 26 cc. of 'water arediazotized with 1 g. NaNO in 20 cc. of water, and the solution isfiltered. The solution is then poured, during 30 minutes, in a mixtureof 350 cc. of glacial acetic acid saturated with S0 with 8.2 g. offinely ground copper chloride powder, keeping the temperature about 7.The mixture is then kept at 10 during 5 minutes and is filtered. It iswashed with water, dried and crystallized from methanol. 21 g. ofsulphonyl chloride are obtained, melting at 6870. An analytical samplehas M.P. 71.5.

Analysis.For CnHnNzClOgS. Calc.: 11.18.

6 g. of this substance are boiled during 50 with 12 cc. of water,decolored with charcoal, and evaporated to dryness under reducedpressure. The residue is washed with hexane and crystallized fromchloroform. The acid crystallizes with two molecules of water and meltsat -6.

Analysis.-For C H N O S. Found: C. 43.08; H, 5.23; S, 10.44. Calc.: C,43.41; H, 5.29; S, 10.53.

EXAMPLE 16 3-p-ethyl-sulphonamideophenyl-S-ethyl-1,2,4 oxadiazole 55 g.of 3-p-aminophenyl-5-ethyl-1,2,4-oxadiazole are dissolved in 89 cc. ofconcentrated HCl and 45 cc. of water. To this solution is added asolution of 21.5 g. of sodium nitrite in 35 cc. of water with cooling.The solution of the diazonium salt is filtered and is added in about 10minutes to a mixture of 525 cc. of glacial acetic acid saturated with S0and 14.4 g. of copper chloride keeping the temperature at about 5. Whenthe addition is complete, the mixture is kept at 10 during about onehour; then there is added one third of its volume of iced water and theprecipitate is recovered. The sulphonyl chloride prepared by this methodand crystallized from methane weighs 26 g. and has a M.P. of 81.

Analysis.For C H ClN O S. S Found: 11.54. Calc.: 11.74.

10 g. of the sulphonyl chloride obtained are dissolved in 200 cc. ofanhydrous benzene. This solution is added to a solution of 7.2 g. ofethylamine in benzene, and the mixture is warmed to 60. After removing.the solvent, the residue is taken up with anhydrous ether and theinsoluble is filtered off. The solvent is again removed and the residueis crystallized from 50% methanol, 6.7 g. of 3 p ethyl sulphonamidophenyl 5 ethyl 1,2,4- oxadiazole are obtained. M.P.

Analysis.For C H N O S. Found: 5.07. Cale. C, 51.24; H, 5.28.

EXAMPLE 17 3-m-sulpham0y[phenyl-S-methyl-1,2,4-0xadiazole A solution of3.1 g. of acetyl chloride in 35 cc. of acetone is added with stirring toa mixture, cooled with iced water, of 6.3 g. ofsulphamoyl-benzamidoxime, 2.8 g. of anhydrous potassium carbonate andcc. of anhydrous acetone. The mixture is then stirred during 4 morehours 'at room temperature. The solid precipitate is fil- S Found:10.92.

tered and is put together with more product obtained by removing thesolvent under reduced pressure, washed with water, and dried undervacuum.

The O-acetyl derivate obtained in this way may be directly cyclized.This is eflected by warming to 240 at 40 mm. until water is evolved;3-trn-sulphamoylphenyl- S-methyl-1,2,4-oxadiazole is obtained andcrystallized from alcohol. 4 g. of product having M.P. 154-6 areobtained.

Analysis.For C H N O S. S Found: 13.45. Calc.: 13.40.

EXAMPLE 18 3-m-sulpham0ylphenyl-S-methyl-1,2,4-0xadiaz0le A suspensionis made in 100 g. of anhydrous acetone of 65 g. ofp-sulphamoyl-benzamidoxime and 2.2 g. of anhydrous potassium carbonate.With stirring and cooling 2.5 g. of acetyl chloride dissolved in 25 cc.of anhy drous acetone are added to the suspension. After stirring during4 hours at room temperature the separated solid is filtered and puttogether with more product obtained by removing the solvent at reducedpressure. The product is washed with water and dried under vacuum. TheO-acetyl-p-sulphamoyl-benzamidoxime crystallizes from alcohol and meltsat 155-6 (with decomposition).

Analysis.-For C H N O S. S Found: 12.50. Calc.: 12.46.

From this compound, heating at 210 at 20 mm. until no more water isevolved, 3-p-sulphamoyl-phenyl-5- methyl-1,2,4-oxadiazole of M.P. 213-4"is obtained with good yield.

Bigzzlysia-For C H N O S. S Found: 13.48.

Calc.:

EXAMPLE 20 3-m-sulphamoylphenyl-5 -prpyl-1 ,2,4-oxadiaz0le 8.6 g. ofsulphamoylbenzamidoxime and 2.9 g. of anhydrous potassium carbonate in150 cc. of anhydrous acetone are reacted with 4.5 g. of butirylchloride, dissolved in 30 cc. of acetone. TheO-butiryhp-sulphamoylbenzamidoxime is obtained with almost theoricyield; it crystallizes from alcohol and melts at 182 (by decomposing).

lzalysisr-for C H N O S. SFound: 11.03. Calc.: 1

The compound thus obtained is cyclized by heating at 180 at 20-30 mm.The solid 3-m-sulphamoylpheny1-5- propyl-l,2,4-oxadiazole is obtainedreadily by dissolving in diluted sodium hydroxide and acidifying. Thecompound crystallized from water melts at 9899. Yield 4.6 g.

Analysis.-For C H N O S: S Found: 11.96. Calc.: 11.99.

EXAMPLE 21 Sodium 3- [3 '-(1 ',2',4'-0xadiaz0yl-5 '-methyl benzenesulphonate 3.2 g. of 3-phenyl-5-methyl1,2,4-oxadiazole are added littleby little to cc. of sulphuric acid containing 20% of S0 The mixture iswarmed to 140, then cooled and added to 40 cc. of saturated NaClsolution cooled with iced water. Thus the sodium salt of the sulphuricacid is recovered, filtered, washed with a cold concentrated solution ofNaCl and dried. 5.8 g. of substance are obtained, and may becrystallized from alcohol.

The sodium salt crystallizes with two molecules of water.

Analysis. For C9H7N204SH3.2H20. Found: N, S, 10.60. Calc.: N 9.39; S10.74. To obtain the free sulphonic acid, the hot alcoholic solution ofthe sodium salt is acidified with hydrochloric acid. The inorganic saltis removed by filtering it 011, and then the solvent is removed. Theacid crystallizes from ethyl acetate and melts at 99-100".

EXAMPLE 22 3-p-carb0xyphenyl-5 -is0butyl-1 ,2,4-0xadiaz0le To a solutionof 15.7 g. of p-ca-rbethoxybenzamidoxime in 300 cc. of anhydrous acetoneare added 6.2 g. of anhydrous potassium carbonate. With stirring andcooling 3. solution of 11 g. of isovaleryl chloride in 100 g. anhydrousacetone is slowly added to the mixture, which is kept under stirring forthree more hours at room temperature. The solvent is removed at reducedpressure and the residue is accurately washed with 'water and dried in adesiccator.

18.5 g. of isovaleryl p-carbethoxybenzamidoxime which melts at 129131are obtained.

Analysis.-For C H N O 9.58.

This compound is warmed during 30 minutes at and 30 mm. of pressure andis successively distilled at reduced pressure.

14.4 g. of 3 p-carbethoxy-phenyl-S-isobutyl-1,2,4-oxadiazole, boiling at138 at 0. 1 mm. are obtained.

Analysis.-For C H N O N Found: 10.49. Calc.: 10.21.

5.5 g. of this compound are dissolved in 10 cc. of absolute alcohol andadded to a solution of 1.2 g. of NaOH in 30 cc. of absolute alcohol. Themixture is refluxed during one and a half hours, the solvent is removedand the residue is taken up with water.

By acidifying with dilute HCl a colourless substance separates, isfiltered, washed and crystallizes from alcohol. 4.5 g. of3-p-carboxyphenyl-S-isobutyl-1,2,4-oxadiazole are obtained. M.P. 17980C.

Analysis.For C H N O -N Found: 11.75. Calc.: 11.38.

According to procedures similar to those described in the precedingexamples the following compounds have also been prepared:

3-p-nitrophenyl-5-ethyl-1,2,4-oxadiazole. M.P. 1067 for C H N O Found:C, 54.60; H, 4.06. Calc.: C, 54.79; H, 4.14.

3-m-nitrophenyl-5-butyl-1,2,4-ox-adiazole. B.P. for C H N O N Found:17.27. Calc.: N 17.00.

3-p-nitrophenyl-5-isobuty1-1,2,4-oxadiazole. B.-P. 0.2- 144 forC I-I N ON Found: 16.76. Calc.: 17.00.

3-p-aminophenyl-5-methyl-1,2,4-oxadiazole. M.P. 117 HCl M.P. 230 for C HClN O. Cl Found: 16.63. Calc.: Cl 16.75.

3-m-aminophenyl-5-methyl-1,2,4-oxadiazole M.P. 79 HCl M.P. 235 for C HClN O. Cl Found: 16.89. Calc.: Cl 16.75.

3-p-arninophenyl-5-ethyl-1,2,4-oxadiazole M.P. 96 HCl M.P. 199 for C H NOFound: C, 63.53; H, 5.88. Calc.: C 63.47; H 5.86.

3-m-aminophenyl-5-butyl-1,2,4-oxadiazole B.P. 0.03- 145 HCl M.P. 149 forC zH ClN O. Cl Found: 13.73. Calc.: Cl 13.97.

3-m-aminophenyl-5-isobutyl-1,2,4-oxadiazole B.P. 0.02- 133 HCl M.P. forC H ClN O. Cl Found: 13.79. Calc.: 01 13.97.

N Found: 9.79. Calc.:

15. A compoundhaving theformul-a:

3,074,957 1/1963 Sc-haefer et a1. 260-307 FOREIGN PATENTS 1/1961Austria.

12 OTHER REFERENCES Bergmann et 211.: J. Org. Chem. vol 18, page 64,(1953).

Crem et a1.: Organic Chemistry, New York, McGraw- 5 Hill, 1959, pp. 355,365, 367, and 368.

Wiley: ed., Fiveand SiX-Membered Compounds with Nitrogen and Oxygen, NewYork, Interscience Publishers, 1962, pp. 246 and 247.

ALEX MAZEL, Primary Examiner.

HENRY R. JILES, Examiner.

RICHARD J. GALLAGHER, A'ssistantExaminer.

1. A COMPOUND HAVING THE FORMULA: